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1.
Diabetologia ; 66(3): 535-550, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36331598

RESUMEN

AIMS/HYPOTHESIS: Glucagon receptor (GCGR) antagonism ameliorates hyperglycaemia and promotes beta cell regeneration in mouse models of type 2 diabetes. However, the underlying mechanisms remain unclear. The present study aimed to investigate the mechanism of beta cell regeneration induced by GCGR antagonism in mice. METHODS: The db/db mice and high-fat diet (HFD)+streptozotocin (STZ)-induced mice with type 2 diabetes were treated with antagonistic GCGR monoclonal antibody (mAb), and the metabolic variables and islet cell quantification were evaluated. Plasma cytokine array and liver RNA sequencing data were used to screen possible mediators, including fibroblast growth factor 21 (FGF21). ELISA, quantitative RT-PCR and western blot were applied to verify FGF21 change. Blockage of FGF21 signalling by FGF21-neutralising antibody (nAb) was used to clarify whether FGF21 was involved in the effects of GCGR mAb on the expression of beta cell identity-related genes under plasma-conditional culture and hepatocyte co-culture conditions. FGF21 nAb-treated db/db mice, systemic Fgf21-knockout (Fgf21-/-) diabetic mice and hepatocyte-specific Fgf21-knockout (Fgf21Hep-/-) diabetic mice were used to reveal the involvement of FGF21 in beta cell regeneration. A BrdU tracing study was used to analyse beta cell proliferation in diabetic mice treated with GCGR mAb. RESULTS: GCGR mAb treatment improved blood glucose control, and increased islet number (db/db 1.6±0.1 vs 0.8±0.1 per mm2, p<0.001; HFD+STZ 1.2±0.1 vs 0.5±0.1 per mm2, p<0.01) and area (db/db 2.5±0.2 vs 1.2±0.2%, p<0.001; HFD+STZ 1.0±0.1 vs 0.3±0.1%, p<0.01) in diabetic mice. The plasma cytokine array and liver RNA sequencing data showed that FGF21 levels in plasma and liver were upregulated by GCGR antagonism. The GCGR mAb induced upregulation of plasma FGF21 levels (db/db 661.5±40.0 vs 466.2±55.7 pg/ml, p<0.05; HFD+STZ 877.0±106.8 vs 445.5±54.0 pg/ml, p<0.05) and the liver levels of Fgf21 mRNA (db/db 3.2±0.5 vs 1.8±0.1, p<0.05; HFD+STZ 2.0±0.3 vs 1.0±0.2, p<0.05) and protein (db/db 2.0±0.2 vs 1.4±0.1, p<0.05; HFD+STZ 1.6±0.1 vs 1.0±0.1, p<0.01). Exposure to plasma or hepatocytes from the GCGR mAb-treated mice upregulated the mRNA levels of characteristic genes associated with beta cell identity in cultured mouse islets and a beta cell line, and blockage of FGF21 activity by an FGF21 nAb diminished this upregulation. Notably, the effects of increased beta cell number induced by GCGR mAb were attenuated in FGF21 nAb-treated db/db mice, Fgf21-/- diabetic mice and Fgf21Hep-/- diabetic mice. Moreover, GCGR mAb treatment enhanced beta cell proliferation in the two groups of diabetic mice, and this effect was weakened in Fgf21-/- and Fgf21Hep-/- mice. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that liver-derived FGF21 is involved in the GCGR antagonism-induced beta cell regeneration in a mouse model of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Células Secretoras de Glucagón , Ratones , Animales , Glucagón/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Glucagón/metabolismo , Diabetes Mellitus Experimental/metabolismo , Receptores de Glucagón/genética , Modelos Animales de Enfermedad , Hígado/metabolismo , Citocinas/metabolismo , Ratones Endogámicos C57BL
2.
Phys Chem Chem Phys ; 25(36): 24395-24405, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37622343

RESUMEN

The dynamics of polymer chains confined to a periodic cylinder is explored using molecular dynamics simulation and theoretical analysis. The cylinder is divided into two cavities in one periodicity: one cavity consists of a channel of length L1 and diameter D1 and another cavity is a channel of length L2 and diameter D2. For L1 = L2 = L/2, the diffusion coefficient D of a single confined polymer chain decreases rapidly with increase in periodicities L. For a fixed periodicity with L = L1 + L2 = constant, the diffusion coefficient D of a single confined polymer chain shows strong dependence on L1 (or L2). Moreover, for a multi-chain system with L1 = L2, the diffusion coefficient D shows strong non-monotonic dependence on the chain monomer density ρ, and the confined polymer chains diffuse fastest for ρ = 0.068, in which there are three polymer chains in two periodicities as well as two opposing effects: one is that the excluded volume effect between polymer chains can reduce the free energy barrier, and another is that when the chain monomer density ρ increases further, the entanglement effect increases, which leads to that the diffusion coefficient D decreases as ρ increases. Finally, we found that the diffusion coefficient D has a similar oscillation relationship with the ratio of R/L for different chain lengths N and different periodicity L, and the oscillation amplitude decreases gradually as R/L increases; here R is the mean end-to-end distance of a single confined polymer chain, i.e., . From the view of free energy potential, both the width of the free energy potential well and the height of the free energy potential barrier govern simultaneously the diffusion behavior of confined polymer chains. According to the mean force potential (PMF) based on the weighted histogram analysis method (WHAM), we found that our results agree very well with the theoretical analysis using the Lifson-Jackson formula. Our investigation may help us understand the dynamics of particles in a periodic medium, which is one of the interesting problems in many different fields of science, such as physics, chemistry and biology.

3.
Soft Matter ; 17(9): 2557-2567, 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33514985

RESUMEN

The sliding dynamics of one- or multi-ring structures along a semiflexible cyclic polymer in radial poly[n]catenanes is investigated using molecular dynamics simulations. The fixed and fluctuating (non-fixed) semiflexible central cyclic polymers are considered, respectively. With increasing bending energy of the central cyclic polymer, for the fixed case, the diffusion coefficient increases monotonically due to the reduction of the tortuous sliding path, while for the fluctuating case, the diffusion coefficient decreases. This indicates that the contribution of the polymer fluctuation is suppressed by a further increase in the stiffness of the central cyclic chain. Compared with the one ring case, the mean-square displacement of the multiple rings exhibits a unique sub-diffusive behavior at intermediate time scales due to the repulsion between two neighboring rings. In addition, for the multi-ring system, the whole set of rings exhibit relatively slower diffusion, but faster local dynamics of threading rings and rotational diffusion of the central cyclic polymer arise. These results may help us to understand the diffusion motion of rings in radial poly[n]catenanes from a fundamental point of view and control the sliding dynamics in molecular designs.

4.
Neoplasma ; 68(3): 490-497, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33502889

RESUMEN

SH2B1, an adaptor protein associated with obesity, is closely related to the occurrence and development of a variety of tumors. To investigate the clinical significance of SH2B1 in colorectal cancer (CRC), expression of SH2B1 in colorectal normal tissues, adenomas, paracarcinoma tissues, carcinoma tissues, and metastatic tissues from 1003 CRC patients was detected by immunohistochemistry (IHC). The prediction power of SH2B1 for CRC prognosis was evaluated by Kaplan-Meier survival analysis and Cox regression model. Results revealed the expression of SH2B1 in carcinoma tissues was significantly higher than that in other tissues. High expression of SH2B1 was an independent risk factor for both disease-free survival (DFS) and disease-specific survival (DSS) and predicted unfavorable prognosis of CRC as well as poor chemotherapeutic response. Conclusively, SH2B1 can serve as an effective predictor for CRC survival and chemotherapeutic outcomes.


Asunto(s)
Neoplasias Colorrectales , Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores de Tumor , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Pronóstico
5.
Lipids Health Dis ; 19(1): 155, 2020 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-32593309

RESUMEN

BACKGROUND: Previous studies have suggested that abnormal sleep duration is associated with increased risk of metabolic syndrome (MetS). However, evidence on the association of sleep duration with stroke, myocardial infarction (MI) and tumors in populations with MetS is limited. METHODS: A total of 8968 participants (2754 with MetS at baseline) were recruited in this retrospective study between March 2012 and December 2012. The baseline characteristics and information on sleep duration were collected by self-reported questionnaires. In addition, physical examination and blood test were also performed. The outcome events in this study were new onset of stroke, MI and tumors during subsequent follow-up. Multivariate logistic regressions were adopted to investigate the relationships between sleep duration and outcome events among different sleep duration groups (< 6 h, 6-7 h, 7-8 h [reference], 8-9 h, and > 9 h per day) in participants with MetS. RESULTS: The mean self-reported total sleep duration was 7.8 ± 1.2 h. Compared with participants with MetS slept for 7-8 h per day, the adjusted odds ratios (ORs) for those slept for > 9 h in stroke, MI and tumors were 2.014 (95% confidence interval [CI]: 1.184-3.426, P = 0.010), 1.731 (95% CI: 0.896-3.344, P = 0.102) and 2.159 (95% CI: 0.991-4.704, P = 0.053), respectively, whereas the adjusted ORs for those slept for < 6 h in stroke, MI and tumors were 2.249 (95% CI: 0.973-5.195, P = 0.058), 1.213 (95% CI, 0.358-4.104, P = 0.756) and 1.743 (95% CI, 0.396-7.668, P = 0.462), respectively. CONCLUSIONS: Long sleep duration (> 9 h) significantly increased the risk of stroke but not MI and tumors in individuals with MetS compared with 7-8 h of sleep duration. Short sleep duration (< 6 h) was not associated with the increased risk of stroke, MI and tumors in individuals with MetS.


Asunto(s)
Síndrome Metabólico/complicaciones , Infarto del Miocardio/etiología , Neoplasias/etiología , Sueño/fisiología , Accidente Cerebrovascular/etiología , Anciano , Índice de Masa Corporal , Femenino , Humanos , Lípidos/sangre , Masculino , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Triglicéridos/sangre
6.
Soft Matter ; 14(25): 5205-5212, 2018 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-29888771

RESUMEN

Effective forces between two micro-wedges immersed in an active bath are investigated using Brownian dynamics simulations. Two anti-parallel and parallel wedge-like obstacles are considered respectively, and the effective forces between two wedges rely on the wedge-to-wedge distance, the apex angle of the wedge, as well as the particle density and aspect ratio. For two anti-parallel wedges, a transition from repulsion to attraction occurs by varying the apex angle, which is also sensitive to the particle density and aspect ratio. The optimal apex angle θr* (or θa*) and particle density ρ* are characterized by the saturated trapping of active particles inside a wedge. For two parallel wedges, the effective force also experiences a transition from repulsion to attraction as the wedge-to-wedge distance increases. These results originate from the collective trapping effect which is driven by the many-body dynamics of self-propelled particles in the confinement (near the boundary) of obstacles. Our results can provide insight into controlling the motion and assembly of microscopic objects through the suspension of active particles.

7.
Soft Matter ; 14(48): 9838-9846, 2018 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-30475363

RESUMEN

With the increase in popularity of 3D printing, an important question arises as to the equivalence between devices manufactured by standard methods vs. those presenting with identical bulk specifications, but manufactured via fused deposition modeling (FDM) printing. Using thermal imaging in conjunction with electron and atomic force microscopy, we demonstrate that large thermal gradients, whose distribution is difficult to predict, are associated with FDM printing and result in incomplete fusion and sharkskin of the printing filament. Even though these features are micro or submicron scale, and hence may not interfere with the intended function of the device, they can have a profound influence if the device comes in contact with living tissue. Dental pulp stem cells were cultured on substrates of identical dimensions, which were either printed or molded from the same PLA stock material. The cultures exhibited significant differences in plating efficiency, migration trajectory, and morphology at early times stemming from attempts by the cells to minimize cytoplasm deformation as they attempt to adhere on the printed surfaces. Even though biomineralization without dexamethasone induction was observed in all cultures at later times, different gene expression patterns were observed on the two surfaces. (Osteogenic markers were upregulated on molded substrates, while odontogenic markers were upregulated on the FDM printed surfaces.) Our results clearly indicate that the method of manufacturing is an important consideration in comparing devices, which come in contact with living tissues.

8.
Med Sci Monit ; 21: 1115-23, 2015 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-25890491

RESUMEN

BACKGROUND: The role of matrix metalloproteinase 9 (MMP-9) polymorphisms in breast cancer risk remains unclear. The purpose of this study was to evaluate the association between MMP-9 variants and breast cancer susceptibility. MATERIAL AND METHODS: Case-control studies were searched on electronic databases to retrieve related articles published between 2000 and 2014 concerning the role of MMP-9 variants in breast cancer risk. Pooled odds ratios (OR) with correlative 95% confidence intervals (CI) were employed to assess this association. RESULTS: Ten articles were screened out, including 6177 breast cancer patients and 6726 matched-controls. For rs3918242 (-1562 C/T), 6 studies contained 1435 patients and 1446 controls. Although the frequency of risk allele C was higher in breast cancer patients than in controls, only TT genotype in recessive model was significantly associated with increased risk of breast cancer (TT vs. CT+CC: OR=1.55, 95% CI=1.12-2.16, P=0.009) in a fixed-effects model. This significant relationship was not observed in other genetic models (P>0.05). No significant association was found between breast cancer risk and rs17576, rs2250889, and rs3787268 under any genetic models. CONCLUSIONS: Our results show that TT genotype of MMP-9-1562 C/T polymorphism might be a risk factor for breast cancer. More studies are needed to further explore this association.


Asunto(s)
Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo de Nucleótido Simple/genética , Alelos , Femenino , Genes Dominantes , Genes Recesivos , Estudios de Asociación Genética , Homocigoto , Humanos , Modelos Genéticos , Sesgo de Publicación , Factores de Riesgo
9.
Soft Matter ; 10(38): 7661-8, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25144601

RESUMEN

Through the molecular dynamics simulation method, we demonstrate that long semi-flexible polymer chains can serve as an effective soft elastic medium for manipulating the ordered structures of small numbers of building blocks, which can be easily controlled by the chain bending stiffness. For two spherical particles in a polymer-particle mixture, three types of local organization are identified: monomer level tight particle bridging, direct contact aggregation, and dispersion. For small numbers of spherical particles in a polymer-particle mixture, the ordered structures of particles, such as spherical and linear particle aggregations, depend mainly on chain bending stiffness. For non-spherical building blocks, the relative orientations of neighboring building blocks are also strongly affected by chain bending stiffness. These results can help us to understand the complexity of the self-assembly of small numbers of building blocks in polymer-particle mixtures and the gene activity in living cells, as well as to construct novel materials in the nanotechnology field.


Asunto(s)
Modelos Químicos , Simulación de Dinámica Molecular , Polímeros/química
10.
Soft Matter ; 10(27): 4875-84, 2014 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-24866417

RESUMEN

Wrapping and unwrapping behaviors of double-stranded DNA around a positively charged nanosphere in solution are studied by using the coarse-grained molecular dynamics (CGMD) simulation method. When monovalent, divalent and trivalent anions are added to the DNA-nanosphere complex solution, double-stranded DNA binds with a nanosphere owing to strong electrostatic attraction. However, when tetravalent anions are added to the DNA-nanosphere complex solution, local charge inversion is observed for a high anion concentration of tetravalent anions and the double-stranded DNA can be unwrapped from the nanosphere because of the local charge inversion near the nanosphere. Moreover, the helical structure of DNA is damaged when double-stranded DNA wraps around the nanosphere and the helical structure can be rebuilt when the double-stranded DNA unwraps from the nanosphere. This study can help us understand how to control the release of DNA in DNA-nanosphere complexes.


Asunto(s)
ADN/química , Nanosferas/química , Aniones/química , Simulación de Dinámica Molecular
11.
J Chem Phys ; 141(10): 104906, 2014 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-25217950

RESUMEN

The ordered structures of nanorods (NRs) in the semiflexible star polymer/NR mixtures are explored by employing molecular dynamics simulation. The structures of small numbers of NRs can be well controlled by varying the stiffness of semiflexible star polymers. At a moderate binding energy between star polymers and NRs, four completely different structures of small numbers of NRs are observed, including that the side-to-side hexagonal aggregation structures of NRs for flexible star polymers, the partly parallel aggregation structures of NRs and the end-to-end contact parallel aggregation structures of NRs for semiflexible star polymers, and the partial dispersion of NRs for rigid star polymers. Helical conformations of semiflexible star polymers binding with NRs are responsible for the formation of the end-to-end contact parallel aggregation structures for small numbers of NRs. This investigation may provide a possible pathway to develop ''smart'' medium to construct novel materials with high performance.

12.
J Chem Phys ; 140(20): 204912, 2014 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-24880330

RESUMEN

The adsorption-desorption transition of DNA in DNA-dendrimer solutions is observed when high-valence anions, such as hexavalent anions, are added to the DNA-dendrimer solutions. In the DNA-dendrimer solutions with low-valence anions, dendrimers bind tightly with the V-shaped double-stranded DNA. When high-valence anions, such as pentavalent or hexavalent anions, are added to the DNA-dendrimer solutions, the double-stranded DNA chains can be stretched straightly and the dendrimers are released from the double-stranded DNA chains. In fact, adding high-valence anions to the solutions can change the charge spatial distribution in the DNA-dendrimer solutions, and weaken the electrostatic interactions between the positively charged dendrimers and the oppositely charged DNA chains. Adsorption-desorption transition of DNA is induced by the overcharging of dendrimers. This investigation is capable of helping us understand how to control effectively the release of DNA in gene/drug delivery because an effective gene delivery for dendrimers includes non-covalent DNA-dendrimer binding and the effective release of DNA in gene therapy.


Asunto(s)
Adsorción , ADN/química , Dendrímeros/química , Aniones/química , Soluciones/química , Electricidad Estática
13.
Drug Discov Today ; 29(6): 103995, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38670255

RESUMEN

Calcium ion dysregulation exerts profound effects on various physiological activities such as tumor proliferation, migration, and drug resistance. Calcium-related channels play a regulatory role in maintaining calcium ion homeostasis, with most channels being highly expressed in tumor cells. Additionally, these channels serve as potential drug targets for the development of antitumor medications. In this review, we first discuss the current research status of these pathways, examining how they modulate various tumor functions such as epithelial-mesenchymal transition (EMT), metabolism, and drug resistance. Simultaneously, we summarize the recent progress in the study of novel small-molecule drugs over the past 5 years and their current status.


Asunto(s)
Antineoplásicos , Bloqueadores de los Canales de Calcio , Canales de Calcio , Transición Epitelial-Mesenquimal , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Canales de Calcio/metabolismo , Animales , Transición Epitelial-Mesenquimal/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Desarrollo de Medicamentos/métodos , Resistencia a Antineoplásicos , Calcio/metabolismo
14.
Nanoscale ; 16(32): 15396-15404, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39093055

RESUMEN

Modulating the A-site deficiency is a useful method to achieve the exsolution of nanoparticles on the surface of perovskite, improving the catalytic activity. However, rules for designing the deficiency value and its roles on the structure and performance remain unclear. In this study, a wide range of A-site deficiencies of (La0.4Sr0.6)1-αTi0.95Ni0.05O3±Î´ (LSTN, α = 0.00, 0.13, 0.15, and 0.18) titanate perovskite materials was designed to systematically investigate their crystal structure, binding energy, oxygen vacancy concentration, exsolution process, and electrochemical performance. An extremely high conductivity (e.g., 331.75 S cm-1@800 °C, 5% H2/Ar) was obtained in parallel with enhanced catalytical activity in SOFC and SOEC modes. The A-site-deficient samples displayed a higher conductivity, oxygen vacancy concentration, and power output than the stoichiometric samples (α = 0.00). The best maximum power density of 78.74 mW cm-2 and the highest population density of 25 particles per µm2 were obtained on the deficient LSTN with α = 0.13. These findings suggest that LSTN is an exceptionally promising material for solid oxide cell (SOC) electrodes.

15.
J Chem Phys ; 138(21): 214901, 2013 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-23758395

RESUMEN

The self-assembly behaviors and phase transitions of binary nanoparticles (NPs) adsorbed on a soft elastic shell are investigated through molecular dynamics simulation. The conformations of adsorbed binary NPs depend on the bending energy K(b) of elastic shell and the binding energy D0 between the NPs and the elastic shell. The ordered structures of binary NPs are observed at the moderate adhesive strength and bending energy, in which the small NPs are located near the vertices of regular pentagons as well as the large NPs are distributed along the sides of the regular pentagons. The shape of soft elastic shell can be adjusted by adding the adsorbed binary NPs, and this investigation can provide an effective way to regulate and reshape surfaces or membranes with the sizes in the micrometer range or smaller.


Asunto(s)
Nanopartículas/química , Adsorción , Simulación de Dinámica Molecular , Transición de Fase , Propiedades de Superficie
16.
J Chem Phys ; 138(9): 094907, 2013 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-23485326

RESUMEN

The phase behavior of cyclic rod-coil diblock copolymer melts is investigated by the dissipative particle dynamics simulation. In order to understand the effect of chain topological architecture better, we also study the linear rod-coil system. The comparison of the calculated phase diagrams between the two rod-coil copolymers reveals that the order-disorder transition point (χN)ODT for cyclic rod-coil diblock copolymers is always higher than that of equivalent linear rod-coil diblocks. In addition, the phase diagram for cyclic system is more "symmetrical," due to the topological constraint. Moreover, there are significant differences in the self-assembled overall morphologies and the local molecular arrangements. For example, frod = 0.5, both lamellar structures are formed while rod packing is different greatly in cyclic and linear cases. The lamellae with rods arranged coplanarly into bilayers occurs in cyclic rod-coil diblocks, while the lamellar structure with rods arranged end by end into interdigitated bilayers appears in linear counterpart. In both the lamellar phases, the domain size ratio of cyclic to linear diblocks is ranged from 0.63 to 0.70. This is attributed to that the cyclic architecture with the additional junction increases the contacts between incompatible blocks and prevents the coil chains from expanding as much as the linear cases. As frod = 0.7, the hexagonally packed cylinder is observed for cyclic rod-coil diblocks, while liquid-crystalline smectic A lamellar phase is formed in linear system. As a result, the cyclization of a linear rod-coil block copolymer can induce remarkable differences in the self-assembly behavior and also diversify its physical properties and applications greatly.


Asunto(s)
Simulación de Dinámica Molecular , Polímeros/síntesis química , Polímeros/química
17.
J Chem Phys ; 139(10): 104901, 2013 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-24050359

RESUMEN

The self-assembly of diblock copolymer (DBCP)/diblock nanorod (DBNR) mixtures are studied by using a dissipative particle dynamics simulation method. The microstructures of DBCP/DBNR blends depend on the type of DBCPs as well as the number of DBNRs. For the asymmetric DBCPs of A3B7, the morphological transition of DBCP/DBNR blends from cylinder phase to lamellar phase is observed for the DBNRs with suitable length and component. Meanwhile, for the symmetric DBCPs of A5B5, the lamellar morphologies of DBCP/DBNR blends can always maintain during the process of adding DBNRs to the blends except for the case of component length mismatch between the DBCPs and the DBNRs. On the other hand, DBCPs can also affect the orientation and the spatial distributions of DBNRs deeply, and the ordered structures of DBNRs are formed for the DBCP/DBNR blends with a large number of DBNRs. Comparisons with homopolymer/DBNR blends are made, and only the aggregation structures are observed in homopolymer/DBNR blends. This investigation can provide valuable assistance in exploring and designing complicated polymer/nanoparticle composites with the desired properties.

18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(3): 397-400, 2013 Mar.
Artículo en Zh | MEDLINE | ID: mdl-23713258

RESUMEN

OBJECTIVE: To observe the effects of deguelin on the apoptosis and proliferation of human esophageal cancer cell Ec-109, and to explore its possible mechanisms. METHODS: Human esophageal cancer cells Ec-109 were in vitro cultured. They were divided into the blank control group, and 5, 10, 20, and 40 nmol/L deguelin groups. The inhibition on the proliferation was detected at 24, 48, and 72 h using CCK-8 assay. The early apoptosis rate at 24 h was detected by flow cytometry. The expressions of apoptosis-related proteins Bcl-2 and Bax were detected at 24 and 48 h respectively. RESULTS: Compared with the blank control group at the same point, the growth inhibition rate in all deguelin groups increased at 24, 48, and 72 h, showing statistical difference (P <0.05). The early apoptosis rate was 4.37% +/- 0.35%, 6.71% +/-0.14%, 15.62% +/- 0.21%, and 19.78% +/- 0.15% in 5, 10, 20, and 40 nmol/L deguelin groups, respectively, showing statistical difference when compared with that of the blank control group (1.10% +/- 0.08%, P < 0.05). Compared with the blank control group, Bcl-2 protein expression obviously decreased, and Bax protein expression obviously increased in 10, 20, and 40 nmol/L deguelin groups, showing statistical difference (P <0.05). The aforesaid indices were in time- and dose-dependent manners. CONCLUSION: Deguelin showed obvious effects on inhibiting the proliferation of Ec-109 cells and promoting their apoptosis, which was correlated with up-regulating Bax protein expression and down-regulating Bcl-2 protein expression.


Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Rotenona/análogos & derivados , Línea Celular Tumoral , Neoplasias Esofágicas/patología , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Rotenona/farmacología , Proteína X Asociada a bcl-2/metabolismo
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(9): 1247-51, 2013 Sep.
Artículo en Zh | MEDLINE | ID: mdl-24273983

RESUMEN

OBJECTIVE: To study the effect of matrine on Fas, VEGF, and activities of telomerase of MCF-7 cells. METHODS: In vitro cultured human breast cancer MCF-7 cells were randomly divided into the experimental group and the control group. The matrine solution was added in cells of the experimental group. Equal volume of culture medium was added in cells of the control group or the negative control group. Zedoary Turmeric Oil, the telomerase inhibitor was added in cells of the positive control group. Morphological changes were observed under an inverted microscope. The telomerase activity was detected by TRAP-ELISA. Expressions of Fas and VEGF protein were detected by immunocytochemical assay. RESULTS: Matrine obviously inhibited the growth and induced apoptosis of breast cancer cells. MCF-7 cells were treated by matrine of different concentrations at 24, 48, and 72 h, the telomerase activity gradually decreased along with increased matrine concentration and prolonged action time, showing dose-effect and time-effect positive relations. Matrine could up-regulate Fas protein expression and downregulate VEGF protein expression of MCF-7 cells. CONCLUSION: Matrine showed obvious effect in inhibiting the growth of MCF-7 cells and promoting the apoptosis, which might be achieved by up-regulating the expression of Fas protein, inhibiting telomerase activity induced apoptosis of breast cancer cells, down-regulating the expression of VEGF protein, and inhibiting the tumor vascular formation.


Asunto(s)
Alcaloides/farmacología , Quinolizinas/farmacología , Telomerasa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor fas/metabolismo , Apoptosis/efectos de los fármacos , Femenino , Humanos , Células MCF-7/efectos de los fármacos , Matrinas
20.
J Phys Chem B ; 127(47): 10189-10200, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-37734004

RESUMEN

In this study, we investigate the sliding dynamics of small charged ring chains along the rigid central cyclic diblock polyelectrolyte of AnBn in radial charged poly[2]catenane in the presence of counterions using molecular dynamics simulations and the Lifson-Jackson formula, and our aim is to study the effects of electrostatical interaction strength, the size of the charged small ring chain, and the rigid block length of the diblock polyelectrolyte on the sliding dynamics of a small ring chain threaded on the rigid diblock polyelectrolyte. The mean-square displacement g3(t) of a small ring chain sliding along the rigid diblock polyelectrolyte of A10B10 exhibits oscillating behavior at short time scales for the moderate electrostatical interaction strength, while for the weak or strong electrostatic interactions, it is normal subdiffusion at short time scales. For n = 1, the diffusion coefficient D of the small ring chain sliding along the rigid diblock polyelectrolyte of A1B1 decreases monotonically as the relative electrostatic interaction strength A increases from A = 0.25-4. However, for n ≠ 1, the diffusion coefficient D of the small ring chain sliding along the rigid diblock polyelectrolyte of AnBn first decreases and then increases with the increase of A, and the nonmonotonous relationship between D and A becomes more obvious for larger n. In view of the free energy potential, the sliding diffusion of a small ring chain is governed by both the width of the free energy potential well and the height of the free energy potential barrier. According to the potential of mean force (PMF) of the small ring chain sliding along the rigid diblock polyelectrolyte, we find that our results are in good agreement with the theoretical analysis using the Lifson-Jackson formula. These results may help us to understand the diffusion motion of a ring chain in radial poly[n]catenanes from a fundamental point of view and control the sliding dynamics in molecular designs.

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